Hydantoins (imidazolidine-2,4-diones) substituted at the 5-position, having the general formula [1], form a class of compounds that is known for almost 135 years after the first disclosure of 5-methylhydantoin ([1], R1═R2═R3═H) by Urech (Ann., 165, 99 (1873)).

Today, 5-substituted hydantoins are versatile building blocks in many synthetic approaches towards a wide variety of medicines and some, like the anticonvulsant 5,5-diphenylhydantoin, have therapeutic properties themselves. One particularly attractive application is the use of hydantoins in multi-enzyme mediated synthesis of enantiomerically pure α-amino acids. For instance, WO 2001/23582 discloses conversion of hydantoins by an Escherichia coli that has been equipped with genetic material encoding the three enzymes hydantoinase, carbamoylase and hydantoin racemase of Arthrobacter aurescens, into enantiomerically pure α-amino acids.
Unfortunately, not all 5-substituted hydantoins are equally well accessible, whereas many of those would be highly desirable as chemical building blocks.
For instance, hydantoins [1] wherein R1 is O-acyl or S-acyl or other O- or S-based leaving groups, form a class of compounds that has not been described, with only one exception, i.e. S-acetylcysteine hydantoin as described by Oh et al. (Archiv der Pharmazie, 328(4), 385-7 (1995)). Likewise, hydantoins [1] wherein R1 is a cyclic alkene, for instance a cyclic enamine, or cyclic keto-alkane group are also unknown. However, this specific class of compounds would be a suitable candidate for the multi-enzyme mediated synthesis of enantiomerically pure α-amino acids as outlined above as the resulting α-amino acids can be used as building blocks for several active pharmaceutical ingredients.
Hence, there is a need for the 5-substituted hydantoins as described above, methods for their preparation and use of these 5-substituted hydantoins in the synthesis of active pharmaceutical ingredients.